Highly Potent Photoinactivation of Bacteria Using a Water-Soluble, Cell-Permeable, DNA-Binding Photosensitizer
- 7 October 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Infectious Diseases
- Vol. 7 (11), 3052-3061
- https://doi.org/10.1021/acsinfecdis.1c00313
Abstract
Antimicrobial photodynamic therapy (APDT) employs a photosensitizer, light, and molecular oxygen to treat infectious diseases via oxidative damage, with a low likelihood for the development of resistance. For optimal APDT efficacy, photosensitizers with cationic charges that can permeate bacteria cells and bind intracellular targets are desired to not limit oxidative damage to the outer bacterial structure. Here we report the application of brominated DAPI (Br-DAPI), a water-soluble, DNA-binding photosensitizer for the eradication of both Gram-negative and Gram-positive bacteria (as demonstrated on N99 Escherichia coli and Bacillus subtilis, respectively). We observe intracellular uptake of Br-DAPI, ROS-mediated bacterial cell death via one- and two-photon excitation, and selective photocytotoxicity of bacteria over mammalian cells. Photocytotoxicity of both N99 E. coli and B. subtilis occurred at submicromolar concentrations (IC50 = 0.2–0.4 μM) and low light doses (5 min irradiation times, 4.5 J cm–2 dose), making it superior to commonly employed APDT phenothiazinium photosensitizers such as methylene blue. Given its high potency and two-photon excitability, Br-DAPI is a promising novel photosensitizer for in vivo APDT applications.Keywords
Funding Information
- Government of Canada
- Natural Sciences and Engineering Research Council of Canada
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